ABCB1 C3435T polymorphism and the lipid-lowering response in hypercholesterolemic patients on statins: a meta-analysis

Lipids in Health and Disease

Jingbo Yu³  Yibo Zheng³  Lindan Ji⁴  Yuan Luo³  Yunyun Zhu³  Qi Yao³  Jianjiang Zhang³  Shujun Yang²  Qinglin Yu¹  Jun Yang³  Hongyu Xu³  Jia Su³ 

[1] Department of Traditional Chinese Internal Medicine, Ningbo No.1 Hospital, Ningbo, Zhejiang Province, People’s Republic of China;Department of Hematology, Ningbo No.1 Hospital, Ningbo, Zhejiang Province, People’s Republic of China;Department of Gerontology, Ningbo No.1 Hospital, Ningbo 315010, Zhejiang Province, People’s Republic of China;Department of Biochemistry, School of Medicine, Ningbo University, Ningbo, Zhejiang Province, People’s Republic of China

关键词: Meta-analysis;    Myopathy;    Serum lipid level;    Statin;    Polymorphism;    ABCB1;   

Others  :  1234410
DOI  :  10.1186/s12944-015-0114-2

 received in 2015-07-09, accepted in 2015-09-02,  发布年份 2015

【 摘 要 】

Background

A number of researches have evaluated the association between the ABCB1 polymorphism and the lipid-lowering response of statins, but the results have been inconclusive. To examine the lipid-lowering efficacy and safety associated with the ABCB1 C3435T polymorphism in hypercholesterolemic patients receiving statin, all available studies were included in this meta-analysis.

Methods

A systematic search for eligible studies in the Cochrane library database, Scopus and PubMed was performed. Articles meeting the inclusion criteria were comprehensively reviewed, and the available data were accumulated by the meta-analysis.

Results

The results indicated that the comparisons of CC+CT vs. TT were associated with a significant elevation of the serum HDL-C levels after statin treatment (CC+CT vs. TT: MD, 2.46; 95 % CI, 0.36 to 4.55; P = 0.02), and the ABCB1 C3435T variant in homozygotes was correlated with decreases in LDL-C (CC vs. TT: MD, 2.29; 95 % CI, 0.37 to 4.20; P = 0.02) as well as TC (CC vs. TT: MD, 3.05; 95 % CI, 0.58 to 5.53; P = 0.02) in patients treated with statin. However, we did not observe a significant association in the TG group or an association between other genetic models serum lipid parameters. In addition, statin treatment more than 5 months led to a higher risk of muscle toxicity.

Conclusions

The evidence from the meta-analysis demonstrated that the ABCB1 C3435T polymorphism may represent a pharmacogenomic biomarker for predicting treatment outcomes in patients on statins and that statin treatment for more than 5 months can increase the risk of myopathy.

【 授权许可】

   
2015 Su et al.

【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

Fig. 5.

Fig. 6.

Fig. 7.

【 参考文献 】

• [1]Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case–control study. Lancet. 2004; 364:937-952.
• [2]Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT et al.. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003; 361:1149-1158.
• [3]Sever PS, Poulter NR, Dahlof B, Wedel H, Collins R, Beevers G, Caulfield M, Kjeldsen SE, Kristinsson A, McInnes GT et al.. Reduction in cardiovascular events with atorvastatin in 2,532 patients with type 2 diabetes: Anglo-Scandinavian Cardiac Outcomes Trial--lipid-lowering arm (ASCOT-LLA). Diabetes Care. 2005; 28:1151-1157.
• [4]Gotto AM. Review of primary and secondary prevention trials with lovastatin, pravastatin, and simvastatin. Am J Cardiol. 2005; 96:34F-38F.
• [5]Bercovich D, Friedlander Y, Korem S, Houminer A, Hoffman A, Kleinberg L, Shochat C, Leitersdorf E, Meiner V. The association of common SNPs and haplotypes in the CETP and MDR1 genes with lipids response to fluvastatin in familial hypercholesterolemia. Atherosclerosis. 2006; 185:97-107.
• [6]Klein I, Sarkadi B, Varadi A. An inventory of the human ABC proteins. Biochim Biophys Acta. 1999; 1461:237-262.
• [7]Fojo A, Lebo R, Shimizu N, Chin JE, Roninson IB, Merlino GT, Gottesman MM, Pastan I. Localization of multidrug resistance-associated DNA sequences to human chromosome 7. Somat Cell Mol Genet. 1986; 12:415-420.
• [8]Kitzmiller JP, Binkley PF, Pandey SR, Suhy AM, Baldassarre D, Hartmann K. Statin pharmacogenomics: pursuing biomarkers for predicting clinical outcomes. Discov Med. 2013; 16:45-51.
• [9]Kajinami K, Brousseau ME, Ordovas JM, Schaefer EJ. Polymorphisms in the multidrug resistance-1 (MDR1) gene influence the response to atorvastatin treatment in a gender-specific manner. Am J Cardiol. 2004; 93:1046-1050.
• [10]Fiegenbaum M, da Silveira FR, Van der Sand CR, Van der Sand LC, Ferreira ME, Pires RC, Hutz MH. The role of common variants of ABCB1, CYP3A4, and CYP3A5 genes in lipid-lowering efficacy and safety of simvastatin treatment. Clin Pharmacol Ther. 2005; 78:551-558.
• [11]Salacka A, Binczak-Kuleta A, Kaczmarczyk M, Hornowska I, Safranow K, Clark JS. Possible association of ABCB1:c.3435T>C polymorphism with high-density-lipoprotein-cholesterol response to statin treatment--a pilot study. Bosn J Basic Med Sci. 2014; 14:144-149.
• [12]Rosales A, Alvear M, Cuevas A, Saavedra N, Zambrano T, Salazar LA. Identification of pharmacogenetic predictors of lipid-lowering response to atorvastatin in Chilean subjects with hypercholesterolemia. Clin Chim Acta. 2012; 413:495-501.
• [13]Rodrigues AC, Rebecchi IM, Bertolami MC, Faludi AA, Hirata MH, Hirata RD. High baseline serum total and LDL cholesterol levels are associated with MDR1 haplotypes in Brazilian hypercholesterolemic individuals of European descent. Braz J Med Biol Res. 2005; 38:1389-1397.
• [14]Shabana MF, Mishriki AA, Issac MS, Bakhoum SW. Do MDR1 and SLCO1B1 polymorphisms influence the therapeutic response to atorvastatin? A study on a cohort of Egyptian patients with hypercholesterolemia. Mol Diagn Ther. 2013; 17:299-309.
• [15]Hoenig MR, Walker PJ, Gurnsey C, Beadle K, Johnson L. The C3435T polymorphism in ABCB1 influences atorvastatin efficacy and muscle symptoms in a high-risk vascular cohort. J Clin Lipidol. 2011; 5:91-96.
• [16]Ferrari M, Guasti L, Maresca A, Mirabile M, Contini S, Grandi AM, Marino F, Cosentino M. Association between statin-induced creatine kinase elevation and genetic polymorphisms in SLCO1B1, ABCB1 and ABCG2. Eur J Clin Pharmacol. 2014; 70:539-547.
• [17]Joy TR, Hegele RA. Narrative review: statin-related myopathy. Ann Intern Med. 2009; 150:858-868.
• [18]Woolf B. On estimating the relation between blood group and disease. Ann Hum Genet. 1955; 19:251-253.
• [19]Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med. 1997; 127:820-826.
• [20]Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003; 327:557-560.
• [21]Sutton AJ, Duval SJ, Tweedie RL, Abrams KR, Jones DR. Empirical assessment of effect of publication bias on meta-analyses. BMJ. 2000; 320:1574-1577.
• [22]Kreisberg RA, Oberman A. Clinical review 141: lipids and atherosclerosis: lessons learned from randomized controlled trials of lipid lowering and other relevant studies. J Clin Endocrinol Metab. 2002; 87:423-437.
• [23]Tanigawara Y. Role of P-glycoprotein in drug disposition. Ther Drug Monit. 2000; 22:137-140.
• [24]Su J, Xu J, Li X, Zhang H, Hu J, Fang R, Chen X. ABCB1 C3435T polymorphism and response to clopidogrel treatment in coronary artery disease (CAD) patients: a meta-analysis. PLoS One. 2012; 7:e46366.
• [25]Garrigues A, Escargueil AE, Orlowski S. The multidrug transporter, P-glycoprotein, actively mediates cholesterol redistribution in the cell membrane. Proc Natl Acad Sci U S A. 2002; 99:10347-10352.
• [26]Tous M, Ribas V, Ferre N, Escola-Gil JC, Blanco-Vaca F, Alonso-Villaverde C, Coll B, Camps J, Joven J. Turpentine-induced inflammation reduces the hepatic expression of the multiple drug resistance gene, the plasma cholesterol concentration and the development of atherosclerosis in apolipoprotein E deficient mice. Biochim Biophys Acta. 2005; 1733:192-198.
• [27]Jeannesson E, Siest G, Bastien B, Albertini L, Aslanidis C, Schmitz G, Visvikis-Siest S. Association of ABCB1 gene polymorphisms with plasma lipid and apolipoprotein concentrations in the STANISLAS cohort. Clin Chim Acta. 2009; 403:198-202.
• [28]Rebecchi IM, Rodrigues AC, Arazi SS, Genvigir FD, Willrich MA, Hirata MH, Soares SA, Bertolami MC, Faludi AA, Bernik MM et al.. ABCB1 and ABCC1 expression in peripheral mononuclear cells is influenced by gene polymorphisms and atorvastatin treatment. Biochem Pharmacol. 2009; 77:66-75.
• [29]Li Q, Hong J, Wu J, Huang ZX, Li QJ, Yin RX, Lin QZ, Wang F. The role of common variants of ABCB1 and CYP7A1 genes in serum lipid levels and lipid-lowering efficacy of statin treatment: a meta-analysis. J Clin Lipidol. 2014; 8:618-629.
• [30]Aydin MU, Aygul N, Altunkeser BB, Unlu A, Taner A. Comparative effects of high-dose atorvastatin versus moderate-dose rosuvastatin on lipid parameters, oxidized-LDL and inflammatory markers in ST elevation myocardial infarction. Atherosclerosis. 2015; 239:439-443.
• [31]Feng Q, Wilke RA, Baye TM. Individualized risk for statin-induced myopathy: current knowledge, emerging challenges and potential solutions. Pharmacogenomics. 2012; 13:579-594.
• [32]Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA. 2003; 289:1681-1690.
• [33]Rosenson RS. Current overview of statin-induced myopathy. Am J Med. 2004; 116:408-416.
• [34]Magni P, Macchi C, Morlotti B, Sirtori CR, Ruscica M. Risk identification and possible countermeasures for muscle adverse effects during statin therapy. Eur J Intern Med. 2015; 26:82-88.
• [35]Amarenco P, Labreuche J. Lipid management in the prevention of stroke: review and updated meta-analysis of statins for stroke prevention. Lancet Neurol. 2009; 8:453-463.
• [36]Simon JA, Lin F, Hulley SB, Blanche PJ, Waters D, Shiboski S, Rotter JI, Nickerson DA, Yang H, Saad M, Krauss RM. Phenotypic predictors of response to simvastatin therapy among African-Americans and Caucasians: the Cholesterol and Pharmacogenetics (CAP) study. Am J Cardiol. 2006; 97:843-850.
• [37]Boccara F, Simon T, Lacombe K, Cohen A, Laloux B, Bozec E, Durant S, Girard PM, Laurent S, Boutouyrie P. Influence of pravastatin on carotid artery structure and function in dyslipidemic HIV-infected patients receiving antiretroviral therapy. AIDS. 2006; 20:2395-2398.
• [38]Al-Sarraf A, Li M, Frohlich J. Statin resistant dyslipidemia in a patient treated with amiodarone. BMJ Case Rep. 2011;2011. doi:10.1136/bcr.08.2011.4620.
• [39]Chen Y, Ku H, Zhao L, Wheeler DC, Li LC, Li Q, Varghese Z, Moorhead JF, Powis SH, Huang A, Ruan XZ. Inflammatory stress induces statin resistance by disrupting 3-hydroxy-3-methylglutaryl-CoA reductase feedback regulation. Arterioscler Thromb Vasc Biol. 2014; 34:365-376.
• [40]Reiner Z. Resistance and intolerance to statins. Nutr Metab Cardiovasc Dis. 2014; 24:1057-1066.
• [41]Reiner Z. Combined therapy in the treatment of dyslipidemia. Fundam Clin Pharmacol. 2010; 24:19-28.
• [42]Blazing MA, Giugliano RP, Cannon CP, Musliner TA, Tershakovec AM, White JA, Reist C, McCagg A, Braunwald E, Califf RM. Evaluating cardiovascular event reduction with ezetimibe as an adjunct to simvastatin in 18,144 patients after acute coronary syndromes: final baseline characteristics of the IMPROVE-IT study population. Am Heart J. 2014; 168:205-212.
• [43]Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015.
• [44]Sabatine MS, Giugliano RP, Wiviott SD, Raal FJ, Blom DJ, Robinson J, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015.
• [45]Dadu RT, Ballantyne CM. Lipid lowering with PCSK9 inhibitors. Nat Rev Cardiol. 2014; 11:563-575.